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Disease Education
Dr. Alvaro Morales

Dr. Alvaro Morales on Bladder Cancer

Dr. Alvaro Morales is the Founding Director of the Centre of Applied Urological Research in the Department of Urology at Queen's University in Kingston, Ontario, Canada and has been a practicing urologist for 40 years.

During the 1970s, Dr. Morales hypothesized that infecting the bladder with live BCG (bacillus Calmette-Guérin, a live vaccine developed in the 1920s to prevent Tuberculosis in humans) would provoke an immune system response that would be sufficiently robust to eliminate some bladder tumours. His pioneering work formed the basis for registration of BCG as a bladder cancer therapy. Since its registration, Dr. Morales has been anticipating a new generation of therapy that would have fewer side effects, better tolerability, and be safer for clinicians to handle.

Dr. Morales has been the Principal Investigator for the Bioniche Phase I and II clinical trials with the Company's technology for bladder cancer , as well as for the first Phase III clinical trial, in which patients with bladder cancer that was refractory (unresponsive) to BCG were treated with the Company's product.

In these video clips, Dr. Morales talks about bladder cancer incidence, treatment options, drawbacks to current therapies, and opportunities for new therapies.

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Video Clips

Incidence of bladder cancer in North America Types of bladder cancer Carcinoma in situ (CIS)

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Please consult your physician for general medical advice Please consult your physician for general medical advice

Bladder Cancer—Malignancy of the Bladder

In its early stages, bladder cancer may not produce any symptoms. If you develop a symptom, it is most likely to be "hematuria," the sight of blood in your urine.   -»

Bladder cancer is strongly associated with cigarette smoking and occupational exposure.  -»

There are several types of bladder cells that can develop into cancer.  -»

The bladder has several layers. Your cancer will be assessed and treated according to how far it has spread into these layers.  -»

Some tumours contain many cells that resemble normal cells, and grow at a slow rate. Others contain many abnormal cells, and grow uncontrollably.  -»

Your cancer will treated according to its, stage and grade. "Stage" is a measure of the extent of the cancer in your body. "Grade" is a measure of how fast the cancer is growing or spreading.  -»

There are several procedures and tests associated with the diagnosis, staging and grading of bladder cancer.  -»

Your treatment will be determined by the stage and grade of your cancer, and your overall health. It may involve a combination of therapies.  -»

Bladder cancer has a high rate of recurrence. Long-term follow-up is essential  -»

"I have been diagnosed with bladder cancer. I need to know more."

When the cells of your bladder-the hollow organ in your body that collects and voids urine from your kidneys-begin to grow out of control and spread to surrounding tissues, you have developed cancer of the bladder.

Bladder cancer develops in the inner lining of your bladder. The type, stage and grade of your cancer will determine the type of treatment that you receive. Bladder cancer that is found in its early stages is highly treatable, and has a high rate of survival. New therapies and improved diagnoses have significantly improved the prognosis for this disease.

Bladder cancer is an increasingly prevalent form of malignancy, especially in industrialized countries. On a worldwide basis, bladder cancer is one of the top 10 leading causes of cancer in men, and one of the top 20 leading causes of cancer in women. In the United States, bladder cancer is one of the top 5 leading causes of cancer in men, and one of the top 10 leading causes of cancer in women. Caucasians are twice as likely as blacks or Hispanics to develop bladder cancer. The lowest rates of bladder cancer occur in Asia and South America.

In its early stages, bladder cancer may not produce any symptoms. If you develop a symptom, it is most likely to be "hematuria," the sight of blood in your urine. Some people experience pain when they urinate, urinary frequency, urinary urgency, or urinary difficulty.

  • Your may notice red or rusty-colored urine every time you urinate, every few times, or just once in a while. The blood may appear one day, and be gone the next-not all bladder cancers bleed steadily.

The medical term for blood in the urine is hematuria, and 80% - 90% of bladder cancer patients have it. There is usually is no pain associated with the blood.

In some cases, you may have blood in your urine that you cannot see. Doctors distinguish between gross hematuria, blood that is visible to the naked eye, and microscopic hematuria, blood that can be seen only under a microscope. About two-thirds of people diagnosed with bladder cancer have gross hematuria, and about one-third are found to have microscopic hematuria when their urine is tested.

If you have hematuria that is associated with cancer, it is not an indicator of the extent of the cancer. In other words, a lot of blood does not necessarily mean that you have a lot of cancer.

If you have noticed blood in your urine, but have not yet consulted your doctor, remember that blood in your urine is not a sure sign of bladder cancer. In fact, it is more likely to be associated with other conditions. But don't ignore it, or just assume that it is a result of bladder infection-bladder cancer that is detected early is much more responsive to treatment.

You should see your doctor if you notice blood in your urine, but keep in mind that hematuria can be caused by a number of other conditions, including strenuous exercise, injury, medications, kidney infection, kidney stones, bladder infection or inflammation (see Cystitis), and bleeding disorders.

  • You may notice changes in your urinary habits. About 20% of bladder cancer patients experience painful urination, increased frequency of urination, or strained or failed attempts to urinate.

You may have to go to the bathroom more often than usual, and you may have to get there quickly-you can't "hold it" for very long. You may have sharp pain, pressure or a burning sensation when you urinate, or you may find that although you feel the urge to urinate, you have to strain to urinate, or produce little or no urine.

Urinary pain, frequency and urgency may be the result of many other health conditions, but be sure to report these symptoms to your doctor. Studies have shown that changes in urinary habits that are caused by bladder cancer are more likely to be associated with bladder carcinoma in situ (also known as CIS or Tis), a flat, lesion-like tumour that can spread to the deeper layers of the bladder and to other parts of your body.

Urinary pain, frequency and urgency do not necessarily indicate bladder cancer. They are symptoms that are commonly associated with many other conditions, including bladder infection and inflammation, bladder stones, kidney infection or disease, neurological disorders, sexually transmitted diseases, endometriosis in women and prostatitis in men.

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Bladder cancer is strongly associated with cigarette smoking, and is also linked to occupational exposure to certain chemicals. Other environmental and genetic risk factors are being investigated.

Smoking: If you are a smoker, you are doubling, and possibly tripling, your odds of developing bladder cancer. In fact, smoking is thought to be the cause of 50% to 66% of bladder tumours in men, and 25% of tumours in women. The longer you smoke, the more you increase your risk.

How does inhaling cigarette smoke affect your bladder? Cancer-causing chemicals in tobacco, such as aromatic amines, are absorbed by your lungs, filtered by your kidneys, and excreted in a concentrated form into your urine. Those toxic compounds are thought to cause abnormal growth in the cells lining your bladder. Researchers have suggested that among people who smoke, those whose bodies are slow to convert cancer-causing compounds to non-toxic chemicals are more likely to develop bladder cancer. This genetic predisposition may help to explain why some smokers get bladder cancer, and others do not.

Historically, the incidence of bladder cancer in women has been only about one third of that in men. Sadly, the rising rate of smoking among women is likely to result in a higher incidence of female bladder cancer.

Smokers can significantly reduce their chances of developing smoking-related bladder cancer by quitting. After only one to four years of not smoking, an ex-smoker's risk of developing the disease falls by 40%.

Occupational Exposure: Heavy exposure to certain chemicals is also linked to an increased risk of bladder cancer. People who work with dyes, rubbers, textiles, paints, plastics, leathers and organic chemicals show a high incidence of the disease. Occupational exposure is thought to account for about 25% of all bladder cancer cases.

"Cyclic chemicals," including benzene derivatives and arylamines are associated with an increased rate of bladder cancer for petroleum and rubber workers, painters, textile workers, truck drivers and aluminum electroplaters.

Hairdressers and barbers are also at risk due to repeated exposure to permanent hair dyes. Even regular (at least once a month), long-term use cosmetic use of permanent hair dyes has been found to be a risk factor for bladder cancer.

Gender is a major risk factor for bladder cancer. Men are 3 to 4 times more likely than women to develop bladder cancer, and 2 to 3 times more likely to die from bladder cancer.

Other Risk Factors: Other associations with an increased risk of bladder cancer have been identified, including:

  • arsenic-contaminated water
  • the intestinal parasite, Schistosoma haematobium (common in Africa)

Other bladder cancer risk factors that have been suggested, but not clearly established, include diesel exhaust, chronic urinary tract infections, chlorine by-products, exposure to the drugs chlornaphazine and cyclophosphamide, pelvic radiation, and pesticides in drinking water.

Studies of caffeine and artificial sweeteners as potential bladder cancer risk factors have found that they are not associated with bladder cancer.

Bladder cancer is primarily a disease of advanced age. Rates in those 70 years and older are about 2 to 3 times higher than those aged 55 - 69 years, and about 15 to 20 times higher than those aged 30 -54 years. In the United States, the average age of diagnosis is 68. Bladder cancer is rare in women under 40, and extremely rare in children.

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There are several types of bladder cells that can develop into cancer. The most common form of bladder cancer is Transitional Cell cancer, which occurs in the "transitional" cells of the bladder lining.

If you have been diagnosed with bladder cancer, chances are it is Transitional Cell Carcinoma, cancer of the "transitional cells" that line your urinary tract, including your bladder. Transitional cells are special cells that are able to change shape, contracting when your bladder empties, and stretching out into a single layer when your bladder fills. Because they line your bladder, your transitional cells come into contact with the waste products in your urine. In industrialized areas, such as North America and Europe, about 90% of all bladder cancers are Transitional Cell Carcinomas (TCC).

Another form of bladder cancer, known as Squamous Cell Carcinoma, accounts for only about 3% of cases in the developed world, but is more common in less developed areas. It is particularly prevalent in the Middle East and in Africa (particularly Egypt), where it is linked to the parasite, Schistosoma haematobium. It is also associated with chronic inflammation, such as that caused by long-term use of a catheter. Squamous cell carcinoma begins in the squamous cells, which are thin, flat cells found in the lining of the bladder.

A third form of bladder cancer, known as Adenocarcinoma, is uncommon, accounting for only 1% -2% of cases. It is a cancer of glandular cells in the lining of the bladder that produce mucus. Other types of bladder cancer, including leiomysocarcomas, rhabdomyosarcomas and pheochromocytomas are extremely rare.

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The bladder has several layers. Your cancer will be assessed and treated according to how far it has spread into these layers. Most bladder cancers are confined to the inner layers of the bladder, and are known as "superficial." Those that spread to outer layers and beyond are called "invasive" cancers.

If you have been diagnosed with bladder cancer, it helps to understand how your bladder is constructed, and where your cancer has developed.

If you were to study a cross-section drawing of your bladder, you would see that your bladder wall is composed of layer upon layer of tissues that surround your bladder's lumen, or hollow area. These many layers can be grouped into four main types of tissue, beginning with the innermost lining of the bladder, and moving to the outermost layer:

  1. The transitional epithelium (also known as the urothelial layer), or inner layer, lined with transitional cells. This is sometimes referred to as the "muscosa."
  2. The lamina propria, a thin zone of connective tissue. This is also known as the "submucosal" layer.
  3. The muscularis propria, a wider zone of smooth muscle tissue. This is sometimes referred to as the "detrusor."
  4. The perivescial fat layer, a zone of fatty connective tissue that surrounds the outside of the bladder, and separates it from other organs. The outside of the bladder is sometimes called the "serosa."

Bladder cancers that are confined to the first two layers of the bladder are known as superficial cancers. About 75% of all bladder cancers are superficial. Although superficial bladder cancers have a tendency to recur (come back after they have been treated or removed), they tend to remain superficial. They also tend to be "non-invasive," with a low risk (less than 20%) of spreading any further.

Cancers that spread into the third layer of muscle tissue, or beyond, are known as invasive cancers. Invasive cancers require more intensive treatment, as they may spread to nearby organs, such as the kidneys, prostate (in men), and uterus and vagina (in women), or to the lymph nodes. The spread of cancer to other areas is called metastasis.

Bladder cancers can vary in shape, size and the number of abnormal cells that they contain. It is possible to have more than one tumour, and more than one type of tumour, at the same time.

  • Papillary tumours are narrow, finger-like or wart-like projections that grow from the bladder lining into the hollow centre of the bladder. Their appearance is sometimes described as frond-like, flower-like, or shaped like a sea anemone.

    Most types of papillary tumours grow only toward the centre and do not spread into, or "invade" the inner layers of the bladder. If left untreated, a small number of papillary tumours invade the bladder wall and spread to other parts of the body. Papillary tumours are the most common type of bladder tumour. They are relatively easy to remove, but they have a tendency to grow back, usually within two years. Patients with large, multiple papillary tumours, as opposed to small, solitary tumours, are more likely to have a recurrence.
  • Solid tumours of the bladder do not occur as often as papillary tumours, but they have a greater rate of recurrence, and a tendency to invade deeply into the bladder wall at an earlier stage.
  • Flat urolethial tumours lie flat against the inner lining of the bladder. They do not grow toward the centre of the bladder. Carcinoma in situ (CIS, or Tis) of the bladder appears as red, inflamed-looking patch or lesion. It is a flat, "non-papillary," surface-spreading tumour. By definition, this type of tumour is confined to the inner layer of the bladder, but it has a higher risk of developing into invasive, usually solid, bladder cancer.

    The size of a CIS tumour does not seem to predict how fast or how far it can spread-if untreated, small CIS tumours can become very invasive (spread deeply), while large tumours may spread slowly, or not at all. CIS tumours are more difficult to detect than papillary tumours, and cannot be easily removed by surgery. For these reasons, CIS tumours are usually regarded as high-risk, and require specialized treatments.

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Some tumours contain many cells that resemble normal cells, and grow at a slow rate. Others contain many abnormal cells, and grow uncontrollably. This is known as "differentiation."

If your bladder tumour contains a lot of cells that resemble the normal cells of your bladder, it is considered to be "well-differentiated." Most superficial, papillary tumours (tumours in the inner layer of the bladder) are well-differentiated. They usually do not grow or spread quickly. "Poorly-differentiated" tumours-cancers with a lot of abnormal cells-are more likely to recur, and to spread. As you might expect, "moderately-differentiated" cells are somewhat likely to recur and spread.

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Your cancer will treated according to its, stage and grade. "Stage" is a measure of the extent of the cancer in your body. "Grade" is a measure of how fast the cancer is growing or spreading.

When you are diagnosed with bladder cancer, your health care team may use a special code to describe your cancer, and to make decisions about treatment. This code will include information about the "stage" and "grade" of your cancer.

Staging: This term refers to the size and location of your cancer, how extensive it is within your bladder, and whether it has spread to tissues around your bladder or to other parts of your body. It is sometimes referred to as "depth of invasion." The most commonly used staging system is known as the "TNM system." It describes where the cancer is in your bladder ("T"), the extent of your lymph node involvement ("N"), and the extent of evidence of metastasic disease, or distant spread ("M").

The "T" (tumour) designation can range from "TX" and "TO," in which the tumour cannot be assessed, or there is no evidence of a primary tumour, all the way to "T4b," in which a tumour has developed, invaded the bladder and spread into the pelvic or abdominal wall. There are usually ten "steps" on the "T" scale, corresponding to the many layers of the bladder, and beyond. The most common bladder tumours are "Ta"-papillary tumours that have not invaded the bladder wall. Carcinoma in situ, a flat tumour that spreads over the surface of the bladder lining, is known as "Tis."

The "N" (lymph node) includes five levels, ranging from NX (cannot be assessed) and "N0" (no evidence of movement into lymph nodes) to "N3" metastasis (movement outside the bladder) in a lymph node more than 5 centimeters in greatest dimension.

The "M" (distant metastasis) designation includes three levels, "MX," in which the presence of distant metastasis cannot be assessed, "M0," in which there is no evidence of distant metastasis, and "M1," in which distant metastasis has occurred.

For example, a tumour that is staged as "Ta N0 M0" is a papillary tumour on the innermost lining of bladder that has not spread to any lymph nodes or any other part of the body.

The stage of your cancer is the most important factor in determining the treatment that you will receive.

Grading: The grade of your tumour is determined by the results of your bladder biopsy. The grade indicates how fast the cancer is thought to be growing, and how aggressively it is thought to be spreading. "High-grade" tumours grow faster, and spread earlier and farther, than "low-grade" tumours. The "differentiation" of the tumour cells, as described above, is a grading factor.

Most grading system use three grades-well-differentiated (Grade I), moderately-differentiated (Grade II) and poorly-differentiated (Grade III), although a four-grade system is sometimes applied. The second number of a grade will indicate which system is used, for example, "I/III,' or "II/IV."

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There are several procedures and tests associated with the diagnosis, staging and grading of bladder cancer, including patient history, physical examination, cystoscopy, biopsy, a variety of urine and blood tests, and several kinds of imaging studies.

  • Your doctor may ask you about your symptoms, and review your medical history and smoking and occupational history. A physical examination may include an internal examination of your rectum or vagina.
  • You may be asked to provide urine specimens (samples) for urinalysis, to look for blood in the urine (microsopic hematuria); urine culture, to look for signs of infection; urine cytology, to look for the presence of cancer cells; and possibly, urinary marker tests, to look for the presence of certain proteins and antigens that are associated with bladder tumours. Urinary marker tests are not yet used routinely, and may be reserved for testing related to cancers that have recurred (returned).
  • You may be asked to undergo a bladder wash, or instillation, in which your bladder is filled with a solution and drained, using a narrow tube called a catheter. Samples of the drained solution are analyzed for the presence of cancer cells. This procedure is an alternative to cytological testing of voided urine specimens.
  • Your doctor may order a painless intravenous pyelogram (IVP), in which a special dye is injected into your bloodstream (usually in your arm) and x-rays are taken to obtain a picture of your urinary tract, including your kidneys, ureters, bladder and urethra. As the dye moves through your urinary tract, a series of x-rays tracks its progress. The IVP test can show abnormalities in your urinary system, and how quickly and efficiently you can handle urinary waste. In some cases, ultra-sound testing may be used in place of the IVP.
  • Your doctor may order a cystoscopy as the main procedure for determining the presence of bladder cancer. Cystoscopy is usually performed as a hospital out-patient procedure (you will be admitted and sent home on the same day). You will receive a general anesthetic, or a local anesthetic that will numb the nerves in your urinary and pelvic area. An instrument known as a cystoscope-a thin, flexible tube equipped with lenses and a light-will be inserted into your bladder through your urethra. (The anesthetic will ensure that this procedure is not painful.) Your bladder will be examined for tumours and other irregularities, and any findings will be noted.
  • During the cystoscopic examination, a biopsy may be performed, in which the cystoscope is used to remove tissue samples from your bladder. The samples will be examined for cancerous cells.
  • Based on the results of these tests, you may be asked to undergo one or more imaging tests, including computerized tomography (CT scan), magnetic resonance imaging (MRI). liver and bone scans, and chest x-ray. Imaging tests, which have varying levels of accuracy, are to assist in the staging of any cancer detected by looking for the presence of cancer in other parts of your body.

The interpretation of diagnostic tests for bladder cancer can be challenging. For example, a lack of blood in urine specimens does not rule out cancer, since tumours may not bleed consistently. Urine cytology-the examination of urine for cancer cells-may be positive, while a cystoscopic examination of the bladder may be negative, indicating that cancer may be present elsewhere in the urinary tract. A tumour that appears to be low-grade during cystocopic examination may prove to be high-grade when tissue samples obtained through biopsy have been examined. Several test results must be combined to determine whether you have cancer, and to accurately assess the type, stage and grade of any tumours that are found.

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Your treatment will be determined by the stage and grade of your cancer, and your overall health. It may involve a combination of therapies.

When you are diagnosed with bladder cancer, your health care team will design a treatment plan with three goals:

  • Remove or destroy as much of the cancer as possible.
  • Prevent or postpone the recurrence (return) of the cancer.
  • Prevent the progression (spread) of the cancer to other parts of your bladder and other parts of your body.

Reaching these goals may be as simple as removal of a small, early-stage, superficial papillary tumour under local anesthetic, or as complex as a combination of surgery, radiation therapy and chemotherapy or immunotherapy (biological therapy).

The choice of therapy-or multiple therapies-will be based on the type, stage and grade of your cancer, and on your overall medical condition.

These therapies include:

  • Tumour removal, known as "transurethral resection," or TUR—This procedure, performed under local or general anesthetic, does not involve any surgical incisions. Cystoscopic instruments are introduced to your bladder through the urethra (just as in diagnostic cystoscopy) and used to remove your tumour, or tumours. Your doctor may use a wire loop, an electric current ("fulgeration"), laser therapy, or a combination of methods to ensure that as many cancer cells as possible are removed.

    Tumour removal by itself may be regarded as adequate treatment for small, low-grade superficial tumours that show no sign of invasion to other parts of your bladder. In many cases, however, TUR may be combined with other "adjuvant" (additional) therapies, such as immunotherapy or chemotherapy, to make sure that all cancer cells have been destroyed, and to keep the cancer from coming back.
  • Bladder removal, known as "cystectomy"—Surgery to remove part, or all, of your bladder, as well as some surrounding organs, may be performed when your cancer has invaded the smooth muscle layer ("muscularis propria") of your bladder, or beyond. You will be given a general anesthetic, and an incision will be made in your abdomen.

    In some cases—when a tumour is small and solitary, or when there is no evidence of the flat, spreading tumour carcinoma in situ—a partial or segmental cystectomy may be possible. In this case, only a part of your bladder is removed, and you may be able to continue to urinate normally.

    If you undergo a radical cystectomy, your bladder will be completely removed. The surgery may also include removal of your pelvic lymph nodes and urethra, your prostate and seminal vesicles (if you are male), and your uterus, ovaries, fallopian tubes, and a section of your vagina (if you are female).

    If your bladder is removed, you will require another means of eliminating urine from your body. A urostomy is one of the most common means of doing this. During your surgery, a small section of your bowel is used to join the ureters leading from your kidneys to a "stoma" (abdominal opening) that drains into a watertight bag. The bag collects your urine, and must be emptied regularly.

    In recent years, an alternative to the external urostomy bag has been developed. A new urinary reservoir, sometimes called a continent urinary reservoir, is constructed inside the abdomen, using a section of your intestine. The reservoir is drained by passing a narrow tube, or catheter through a small, easily-concealed opening in your abdomen.

    Some male bladder cancer patients may be eligible for yet another alternative to the urostomy. A neobladder, or interior pouch, is constructed and stitched directly to the urethra, allowing urine to pass normally. This method can be used only when it is certain that there is no high-grade or invasive cancer present in your urethra, or the neck of your bladder.

    Since bladder removal is a drastic and life-altering step, medical experts are working to make bladder preservation a safe and effective alternative to bladder removal. Even if your cancer is invasive, your health care team may recommend a non-surgical treatment plan that use a combination of therapies to prevent or postpone the removal of your bladder.
  • Intravesical therapy, the placement of liquid medication directly into your bladder—Many kinds of bladder "instillations" or "infusions" have been developed as a supplement, or an alternative to tumour removal (TUR) and bladder removal (cystectomy). A treatment agent is introduced to your bladder through a narrow tube, or catheter, passed through your urethra. The agent is held in the bladder for a prescribed amount of time, and drained. The number of treatments will be determined by the agent used, the type of cancer you have, and the stage and grade of your cancer.

    In some cases, such as flat, spreading carcinoma in situ, tumour removal may be difficult or impossible. In other cases, medical conditions and ill health may rule out bladder removal surgery. Intravesical therapy may be the therapy of choice in these instances.

    Intravesical therapy may involve the use of two kinds of treatment agents, immunotherapy, also known as biological therapy, and chemotherapy, the use of drugs to destroy cancer cells.

    Immunotherapy makes use of your body's natural defenses, by stimulating or boosting your immune system to fight and destroy your cancer. Immunomodulating agents, such as bacillus Calmette-Guerin (BCG), originally developed as a vaccine for tuberculosis, trigger an immune response that destroys cancer cells. Biological response modifiers alter the interaction between the body's immune defenses and cancer cells to boost, direct, or restore the body's ability to fight disease.

    You may receive chemotherapy medication as an intravesical therapy, or as a systemic therapy, given orally or intravenously (through a vein). Systemic chemotherapy targets cancer cells throughout your body.
  • Radiation therapy uses high-energy rays to destroy cancer cells. You may receive external beam radiation, emitted from a machine outside your body, or internal radiation, emitted from radioactive "seeds" implanted directly into your tumour.
  • Photodynamic therapy, also known as phototherapy—In this new approach to bladder cancer treatment, a light-sensitive chemical is injected into your body and taken up by your cancer cells. The cancer cells are destroyed when they are exposed to light from a laser beam.

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Bladder cancer has a high rate of recurrence. Long-term follow-up is essential.

Although bladder cancer is highly treatable, it also has an unusually high rate of recurrence compared to other forms of cancer. After initial treatment, you may be advised to have a regular series of follow-up tests and procedures. Typically, your follow-up schedule will include urine testing and cystoscopy every 3 months for the first 2 years, every 6 months for the next 2 years, and yearly in following years.

Be sure to follow your schedule—frequent check-ups can spot new tumours early and prevent the spread of any further disease.

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